'''Liver transplantation''' or '''hepatic transplantation''' is the replacement of a diseased [[liver]] with a healthy liver [[allograft]]. The most commonly used technique is orthotopic transplantation, in which the native liver is removed and the donor organ is placed in the same anatomic location as the original liver. Liver transplantation nowadays is a well accepted treatment option for end-stage liver disease and acute liver failure.

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When a healthy [[liver]] [[allograft]] is used in place of damaged [[liver]] tissue, it is termed as [[liver transplantation]]. Thomas Starzl used dogs as the first animals for [[research]] on liver transplantation in the 1960s. In 1963, the first liver transplant in humans was attempted by Dr. [[Thomas Starzl]] of Colorado, United States. The most common indications for liver transplantation in the United States are [[hepatitis C virus]], [[alcoholic liver disease]], autoimmune [[liver]] disease, [[primary biliary cirrhosis]], [[primary sclerosing cholangitis]], [[hepatitis B virus]], [[liver]] disease due to inborn errors of [[metabolism]], [[cancer]], [[biliary atresia]] and [[acute liver failure]]. On the other hand, absolute contraindications to liver transplantation include [[hepatocellular carcinoma]] with [[metastasis]], [[acute liver failure]] with persistently elevated [[intracranial pressure]] [[Intracranial pressure|ICP]] >50mmHg, [[Angiosarcoma|hemangiosarcoma]], hilar [[cholangiocarcinoma]], [[sepsis]], and active [[alcohol]] or [[drug abuse]]. Pretransplant measures such as cardiopulmonary evaluation, screening for [[Cancer of unknown primary origin|occult cancer]], [[infection]], and [[psychosocial]] evaluation must be performed prior to surgery. The most commonly used technique employed in patients is orthotopic transplantation. This involves removal of the native [[liver]] and placement of the donor organ in the same anatomic location as the original [[liver]]. [[Immunosuppressive agents]] used after transplantation include [[cyclosporine]], [[everolimus]], [[mycophenolate]], [[Corticosteroid|corticosteroids]], [[azathioprine]], and [[tacrolimus]] in different combinations. The most common causes of death in liver transplant patients are [[infection]], [[Cancer|malignancy]], and [[Transplant rejection|rejection]]. It is necessary to monitor [[Patient|patients]] for signs of complications and treat them effectively.

==Liver Transplantation==

==Liver Transplantation==

===History===

===History===

* In the 1960s, Thomas Starzl used dogs as the first animals for [[research]] on liver transplantation in Boston and Chicago.

* In the 1960s, Thomas Starzl used dogs as the first animals for [[research]] on liver transplantation in Boston and Chicago.

* Dr. Starzl performed several additional [[Organ transplant|transplants]] over the next few years before the first short-term success was achieved in 1967 with the first one-year survival post-transplantation.

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* Dr. Starzl performed many additional [[Organ transplant|transplants]] until he was successful in 1967 with the first one-year survival post-transplantation.

* In 1970, the regimen for [[Immunosuppression|immunosuppressive therapy]] following [[Organ transplant|transplant]] was introduced, but [[azathioprine]] and [[Steroid|steroids]] did not improve survival rates of patients.

* In 1970, the regimen for [[Immunosuppression|immunosuppressive therapy]] following [[Organ transplant|transplant]] was introduced, but [[azathioprine]] and [[Steroid|steroids]] did not improve survival rates of patients.

* In the 1980s, with the introduction of [[cyclosporine]] by Sir [[Roy Calne]], there was an improvement in [[Transplant rejection|rejection]] rates.

* In the 1980s, with the introduction of [[cyclosporine]] by Sir [[Roy Calne]], there was an improvement in [[Transplant rejection|rejection]] rates.

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* In 1999, approximately 5000 procedures were carried out, in contrast to 100 which had been performed a decade earlier.

* In 1999, approximately 5000 procedures were carried out, in contrast to 100 which had been performed a decade earlier.

* Liver transplantation is now performed at over one hundred centers in the [[USA]], as well as numerous centers in Europe and elsewhere. One year [[patient]] [[Survival analysis|survival]] is 85-90%, and outcomes continue to improve, although liver transplantation remains a formidable [[Surgery|procedure]] with frequent complications.

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* Unfortunately, the supply of [[liver]] [[allograft]]s from non-living donors is far short of the number of potential recipients, a reality that has spurred the development of [[#Living donor transplantation|living donor liver transplantation]].

* In December 2016, 147,128 liver transplants were performed in the US as compared to 7217 in 1998 based on data from the United Organ Sharing (UNOS) network.

* In December 2016, 147,128 liver transplants were performed in the US as compared to 7217 in 1998 based on data from the United Organ Sharing (UNOS) network.

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===Indications===

===Indications===

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* Liver transplantation is applicable to any acute or chronic condition resulting in irreversible [[liver]] dysfunction, provided that the recipient does not have other conditions that will preclude a successful [[Organ transplant|transplant]].

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Liver transplantation is applicable to any acute or chronic condition resulting in irreversible [[liver]] dysfunction, provided that the recipient does not have other conditions that will preclude a successful [[Organ transplant|transplant]]. Most liver transplants are performed for [[Chronic liver disease|chronic liver diseases]] that lead to irreversible scarring of the [[liver]], or [[cirrhosis]].

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* Most liver transplants are performed for [[Chronic liver disease|chronic liver diseases]] that lead to irreversible scarring of the [[liver]], or [[cirrhosis]].

* The most common indications for liver transplantation in the United States are:

* The most common indications for liver transplantation in the United States are:

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** [[Hepatitis C virus]]

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** [[Hepatitis C]]

** [[Alcoholic liver disease]]

** [[Alcoholic liver disease]]

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** Idiopathic/autoimmune liver disease

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** Idiopathic or autoimmune liver disease

** [[Primary biliary cirrhosis]]

** [[Primary biliary cirrhosis]]

** [[Primary sclerosing cholangitis]]

** [[Primary sclerosing cholangitis]]

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** [[Hepatitis B virus]]

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** [[Hepatitis B]]

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** Metabolic [[liver]] disease (eg, inborn errors of [[metabolism]])

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** Metabolic [[liver]] disease (e.g. inborn errors of [[metabolism]])

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** [[Cancer]]

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** [[Carcinoma]]

** [[Biliary atresia]]

** [[Biliary atresia]]

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** [[Acute liver failure]] :

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** [[Acute liver failure]]:

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*** Severe acute [[liver]] injury with impaired synthetic function of the [[liver]](INR ≥1.5) and [[encephalopathy]] in the absence of pre existing [[liver]] disease or cirrhosis.

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*** Severe acute [[liver]] injury with impaired synthetic function of the [[liver]] (INR ≥1.5) and [[encephalopathy]] in the absence of pre existing [[liver]] disease or cirrhosis

****** [[Hepatocellular carcinoma|HCC]]: a single lesion ≤5 cm or up to three separate [[Lesion|lesions]] all <3 cm, no evidence of gross [[vascular]] invasion, and no regional [[Lymph node|nodal]] or distant [[metastasis]].

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****** [[Hepatocellular carcinoma|HCC]]:

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******* A single lesion ≤5 cm or up to three separate [[Lesion|lesions]] all <3 cm

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******* No evidence of gross [[vascular]] invasion, and

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******* No regional [[Lymph node|nodal]] or distant [[metastasis]]

****** [[Neuroendocrine tumors]] that have metastasized to the [[liver]]

****** [[Neuroendocrine tumors]] that have metastasized to the [[liver]]

Pre-transplant evaluation is particularly aggressive in patients prior to [[Organ transplant|transplantation]] to minimize post operative morbidity and mortality due to effects of surgery and [[Immunosuppression|immunosuppressive therapy]].The following evaluations are required:

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* Cardiopulmonary

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* Screening for [[Cancer of unknown primary origin|occult cancer]]

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* Screening for occult [[infection]]

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* [[Psychosocial|Psychosocial evaluation]]

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==== Laboratory investigations ====

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Laboratory investigations essential for patient evaluation prior to liver transplantation are as follows:

* A major advance in [[Pediatrics|pediatric]] liver transplantation was the development of reduced size liver transplantation, in which a portion of an adult [[liver]] is used for an infant or small child.

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* A major advance in [[Pediatrics|pediatric]] liver transplantation was the development of reduced size liver transplantation, in which a portion of an adult [[liver]] is used for an infant or child.

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* Further developments in this area included split liver transplantation, in which one [[liver]] is used for transplants for two recipients, and [[living donor liver transplantation]], in which a portion of healthy person's [[liver]] is removed and used as the [[allograft]].

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* Further developments in this area included split liver transplantation in which one [[liver]] is used for transplants for two recipients and [[living donor liver transplantation]], in which a portion of the liver of a healthy person is removed and used as the [[allograft]].

* Living [[Blood donation|donor]] liver transplantation for [[Pediatrics|pediatric]] recipients involves removal of approximately 20% of the [[liver]] ([[Couinaud]] segments 2 and 3).

* Living [[Blood donation|donor]] liver transplantation for [[Pediatrics|pediatric]] recipients involves removal of approximately 20% of the [[liver]] ([[Couinaud]] segments 2 and 3).

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===Orthotopic Liver Transplantation===

===Orthotopic Liver Transplantation===

* Donor selection based on [[Cardiac biomarkers|biomarkers]] and risk indices is a crucial aspect of orthotopic liver transplantation and involves:

* Donor selection based on [[Cardiac biomarkers|biomarkers]] and risk indices is a crucial aspect of orthotopic liver transplantation and involves:

* The risk of [[Rejection|chronic rejection]] in [[Patient|patients]] with liver transplantation decreases with time,although recipients may need to take [[Immunosuppresive drug|immunosuppresive therapy]] for the rest of their lives.

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* The risk of [[Rejection|chronic rejection]] in [[Patient|patients]] with liver transplantation decreases with time, although recipients may need to take lifelong [[Immunosuppresive drug|immunosuppresive therapy]]

* In LDLT, a piece of healthy [[liver]] is surgically removed from a living person and transplanted into a recipient, immediately after the recipient’s diseased [[liver]] has been entirely removed.

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* In LDLT, a piece of healthy [[liver]] is surgically removed from a living person and transplanted into a recipient, immediately after the diseased [[liver]] of the recipient has been entirely removed

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* Historically, LDLT was used as a means for parents of children with severe [[liver]] disease to donate a portion of their healthy [[liver]] to replace the damaged [[liver]] of their children.

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* Historically, LDLT was used as a means for parents of children with severe [[liver]] disease to donate a portion of their healthy [[liver]] to replace the damaged [[liver]] of their children

* In 1986, the first successful LDLT was performed at the Universidade de São Paulo (USP) Medical School, by Dr. [[Silvano Raia]].

* In 1986, the first successful LDLT was performed at the Universidade de São Paulo (USP) Medical School, by Dr. [[Silvano Raia]].

* To monitor the [[patient]] for complications, the following investigations are used:

* To monitor the [[patient]] for complications, the following investigations are used:

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==== Laboratory investigations ====

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** Laboratory investigations

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* The following laboratory investigations help in providing evidence of [[Transplant rejection|rejection]], and also help in the assessment of [[:Category:Drugs|drugs]]( [[Azathioprine]], [[Cyclosporine]] and [[Tacrolimus]]) along with their effect on [[bone marrow]] and [[Kidney|renal]] function:

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** [[Complete blood count|CBC]]

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*** The following laboratory investigations help in providing evidence of [[Transplant rejection|rejection]], and also help in the assessment of [[:Category:Drugs|drugs]]( [[Azathioprine]], [[Cyclosporine]] and [[Tacrolimus]]) along with their effect on [[bone marrow]] and [[Kidney|renal]] function:

In December 2016, 147,128 liver transplants were performed in the US as compared to 7217 in 1998 based on data from the United Organ Sharing (UNOS) network.

Indications

Liver transplantation is applicable to any acute or chronic condition resulting in irreversible liver dysfunction, provided that the recipient does not have other conditions that will preclude a successful transplant. Most liver transplants are performed for chronic liver diseases that lead to irreversible scarring of the liver, or cirrhosis.

The most common indications for liver transplantation in the United States are:

Pre-transplant evaluation is particularly aggressive in patients prior to transplantation to minimize post operative morbidity and mortality due to effects of surgery and immunosuppressive therapy.The following evaluations are required:

The surgery usually takes between five and six hours, but may be longer or shorter due to the difficulty of the operation and the experience of the surgeon.

The large majority of liver transplants use the entire liver from a non-living donor for the transplant, particularly for adult recipients.[30][31]

A major advance in pediatric liver transplantation was the development of reduced size liver transplantation, in which a portion of an adult liver is used for an infant or child.

Further developments in this area included split liver transplantation in which one liver is used for transplants for two recipients and living donor liver transplantation, in which a portion of the liver of a healthy person is removed and used as the allograft.

Living donor liver transplantation for pediatric recipients involves removal of approximately 20% of the liver (Couinaud segments 2 and 3).

Orthotopic Liver Transplantation

Donor selection based on biomarkers and risk indices is a crucial aspect of orthotopic liver transplantation and involves: